Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data

Am J Med Genet B Neuropsychiatr Genet. 2018 Oct;177(7):641-657. doi: 10.1002/ajmg.b.32652. Epub 2018 Oct 16.

Abstract

Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.

Keywords: C-reactive protein; Crohn's disease; Tourette syndrome; allergy; anorexia nervosa; attention deficit-hyperactivity disorder; autoimmune disorder; bipolar disorder; celiac disease; childhood ear infection; genetic correlation; genome-wide association; hypothyroidism; major depression; neuroticism; obsessive schizophrenia; primary biliary cirrhosis; rheumatoid arthritis; smoking; systemic lupus erythematosus; tuberculosis susceptibility; type 1 diabetes; ulcerative colitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / physiopathology
  • Comorbidity
  • Databases, Factual
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / methods
  • Humans
  • Linkage Disequilibrium
  • Male
  • Mental Disorders / genetics*
  • Mental Disorders / physiopathology
  • Multifactorial Inheritance
  • Polymorphism, Single Nucleotide